Methodology Special Interest Group
Chair: Dr Jeremy Hobart, Peninsula College of Medicine & Dentistry
Clinical research needs hard outcomes. More than 250 years ago, in 1747, the Scottish naval surgeon James Lind performed the first randomised controlled trial, treating selected scurvy-ridden sailors with lemons and oranges. He obtained dramatic cures in the citrus-treated group, which was pronounced ‘fit for purpose’, enabling sailors to get back to work. This is indeed a hard outcome measure, but unfortunately over the past 250 years, development in the way we do clinical trials has not kept pace with developments in basic science.
- We have virtually no treatments to slow neurodegenerative diseases (ie only one treatment in motor neurone disease that may be neuroprotective)
- Clinical trials to test new drugs are extremely expensive and many billions of pounds spent so far have not led to any treatments to slow the commonest conditions of Parkinson’s and Alzheimer’s disease
- Most of the commonly used measurement methods and instruments fall short of what is required for modern clinical trials
- Most of the measurement instruments take little account of the patient and carer perspective of disease impact on day-to-day activities
- There are many new methods of testing the measuring instruments we currently use and many new ways to develop more modern measurement instruments. These all need to be investigated and introduced into the way we do clinical trials
- If we can find robust ways of measuring disease impact over the short term, which we have confidence reflects disease progression and not just symptom relief, then we can test more drugs that may be useful to slow neurodegenerative diseases
Research priorities and questions
One: why do we only have one drug that slows neurodegeneration? Is it because all our drugs are useless? Or is it that the way we do clinical trials, and the way we measure outcomes, could be much better? There is an urgent need for us to tackle this situation.
Two: how do we separate symptoms from the underlying disease course? Parkinson’s disease specialists know from the DATATOP study that this is of great importance; that treatments seemingly showing evidence of a disease-modifying effect actually had an effect on disease symptoms.
Three: Are our outcome measures up to scratch? This is a very important area. Most outcome measures are currently not based on good qualitative frameworks. They are not good rulers against which we measure the progression of our diseases.
Four: What size of effect is important to patients? Is the size of the effect, to a patient with Parkinson’s disease, the same at the beginning of the disease as at the end? Do we really know what kinds of effects we are looking for, in order to effectively design clinical trials around these effects? We don’t know – but we really do need to.
Five: Current clinical trials are geared towards looking for a big effect, fast – a neurodegenerative ‘eureka’ moment. We need to take a different approach: to build one trial on the results of previous ones so that, eventually, trials lead to cures.
Tracking responders in a heterogeneous condition is difficult, and we need to get much wiser about how we pick up patients that respond to treatment. How do we monitor the responder effect in a sub group of patients? Importantly, we also need to bring the pharmaceutical industry on board. These companies are beginning to seriously question their business model, with only one drug coming to market after all the millions spent on research and development. The pharmaceutical industry simply can’t afford for the work planned for the DeNDRoN SIG not to occur.
List of Methodology SIG members 